Actin assembly ruptures the nuclear envelope by prying the lamina away from nuclear pores and nuclear membranes in starfish oocytes.

The nucleus of oocytes (germinal vesicle) is unusually large and its nuclear envelope (NE) is densely packed with nuclear pore complexes (NPCs) stockpiled for embryonic development. We showed that breakdown of this specialized NE is mediated by an Arp2/3-nucleated F-actin 'shell' in starfish oocytes, in contrast to microtubule-driven tearing in mammalian fibroblasts. Here, we address the mechanism of F-actin-driven NE rupture by correlated live-cell, super-resolution and electron microscopy. We show that actin is nucleated within the lamina sprouting filopodia-like spikes towards the nuclear membranes. These F-actin spikes protrude pore-free nuclear membranes, whereas the adjoining membrane stretches accumulate NPCs associated with the still-intact lamina. Packed NPCs sort into a distinct membrane network, while breaks appear in ER-like, pore-free regions. Thereby, we reveal a new function for actin-mediated membrane shaping in nuclear rupture that is likely to have implications in other contexts such as nuclear rupture observed in cancer cells

Comments on the High Pressure Preservation of Human Milk

The current state of studies on the high pressure preservation of the human milk is briefly presented. It is indicated that reaching (i) the antimicrobial safety, (ii) antiviral safety, and (iii) high nutritional, metabolic and immunological quality, may be difficult for a “classical” single pressure pulse High Pressure Preservation (HPP) treatment. It is shown that the sudden decompression leads to additional physical processes, which can be important for supporting the HPP technology. Additional advantages were reached due to the two-pulse compression, with subsequent values: P = 200 MPa and 400 MPa. Tests included the microbiological insight for the two-weeks storage. It is also shown that the decay of the number of microorganisms under the high pressure follows the relation n(t) = n0exp(At)exp(Bt2). Finally, issues regarding containers for the high pressure preservation of human milk are discussed

Donor human milk in Neonatal Intensive Care Unit — to whom, how much and how long?

Objectives: The aim of the study was to present the variability of patients who received donor human milk (DHM) during Neonatal Intensive Care Unit (NICU) hospitalization, including time of its usage and volume of portions.  Material and methods: A retrospective analysis of data was conducted for all infants admitted to the NICU at the University Hospital during the first year of the Human Milk Bank operation. One-way analysis of variance in the intergroup scheme, Kruskal-Wallis variance analysis with the Jonckheere-Tepstra test, correlation analysis using Pearson’s r and Spearmann’s rho, frequency analysis using the Fisher’s exact test were used to conduct analyses.  Results: 133 newborns received DHM. 3 groups of neonates were identified: < 32 0/7 weeks, 32 0/7–36 6/7 weeks and > 37 0/7 weeks of gestational age (GA). Time of DHM supplementation was similar in all groups and does not differ depending on the GA but preterm infants received the smallest total volume of DHM. However, infants > 37 weeks of GA had almost a threefold greater chance of abandoning breastfeeding than the others (odds ratio (OR) = 2.89, 95% CI: 0.69–12.20). There was a statistically significant, weak negative correlation between period of total parenteral nutrition and the volume of milk from the bank: rho = –0.194; p = 0.026.  Conclusions: The DHM supply did not have a negative impact on lactation and breastfeeding. Stimulation of lactation was necessary for 5–7 days. The time of DHM supply was the same regardless of GA. The majority of infants were breastfed or received only MOM on the day of discharge from the hospital

Integrating microfluidic generation, handling and analysis of biomimetic giant unilamellar vesicles

The key roles played by phospholipids in many cellular processes, has led to the development of model systems, to explore both lipid–lipid and lipid–peptide interactions. Biomimetic giant unilamellar vesicles represent close facsimiles of in vivo cellular membranes, although currently their widespread use in research is hindered by difficulties involving their integration into high-throughput techniques, for exploring membrane biology intensively in situ. This paper presents an integrated microfluidic device for the production, manipulation and high-throughput analysis of giant unilamellar vesicles. Its utility is demonstrated by exploring the lipid interaction dynamics of the pore-forming antimicrobial peptide melittin, assessed through the release of fluorescent dyes from within biomimetic vesicles, with membrane compositions similar to mammalian plasma membranes

IAEA methodology for on-site end-to-end IMRT/VMAT audits : an international pilot study

The IAEA has developed and tested an on-site, end-to-end IMRT/VMAT dosimetry audit methodology for head and neck cases using an anthropomorphic phantom. The audit methodology is described, and the results of the international pilot testing are presented. The audit utilizes a specially designed, commercially available anthropomorphic phantom capable of accommodating a small volume ion chamber (IC) in four locations (three in planning target volumes (PTVs) and one in an organ at risk (OAR)) and a Gafchromic film in a coronal plane for the absorbed dose to water and two-dimensional dose distribution measurements, respectively. The audit consists of a pre-visit and on-site phases. The pre-visit phase is carried out remotely and includes a treatment planning task and a set of computational exercises. The on-site phase aims at comparing the treatment planning system (TPS) calculations with measurements in the anthropomorphic phantom following an end-to-end approach. Two main aspects were tested in the pilot study: feasibility of the planning constraints and the accuracy of IC and film results in comparison with TPS calculations. Treatment plan quality was scored from 0 to 100. Results: Forty-two treatment plans were submitted by 14 institutions from 10 countries, with 79% of them having a plan quality score over 90. Seventeen sets of IC measurement results were collected, and the average measured to calculated dose ratio was 0.988 ± 0.016 for PTVs and 1.020 ± 0.029 for OAR. For 13 film measurement results, the average gamma passing rate was 94.1% using criteria of 3%/3 mm, 20% threshold and global gamma. The audit methodology was proved to be feasible and ready to be adopted by national dosimetry audit networks for local implementation

Pharmacological Blockade of Serotonin 5-HT7 Receptor Reverses Working Memory Deficits in Rats by Normalizing Cortical Glutamate Neurotransmission

The role of 5-HT7 receptor has been demonstrated in various animal models of mood disorders; however its function in cognition remains largely speculative. This study evaluates the effects of SB-269970, a selective 5-HT7 antagonist, in a translational model of working memory deficit and investigates whether it modulates cortical glutamate and/or dopamine neurotransmission in rats. The effect of SB-269970 was evaluated in the delayed non-matching to position task alone or in combination with MK-801, a non-competitive NMDA receptor antagonist, and, in separate experiments, with scopolamine, a non-selective muscarinic antagonist. SB-269970 (10 mg/kg) significantly reversed the deficits induced by MK-801 (0.1 mg/kg) but augmented the deficit induced by scopolamine (0.06 mg/kg). The ability of SB-269970 to modulate MK-801-induced glutamate and dopamine extracellular levels was separately evaluated using biosensor technology and microdialysis in the prefrontal cortex of freely moving rats. SB-269970 normalized MK-801 -induced glutamate but not dopamine extracellular levels in the prefrontal cortex. Rat plasma and brain concentrations of MK-801 were not affected by co-administration of SB-269970, arguing for a pharmacodynamic rather than a pharmacokinetic mechanism. These results indicate that 5-HT7 receptor antagonists might reverse cognitive deficits associated with NMDA receptor hypofunction by selectively normalizing glutamatergic neurotransmission